Cell villages and Dirichlet modeling map human cell fitness genetics.

Cell village and Dirichlet modeling reveal genetic factors influencing human neural progenitor cell proliferation, including autism risk and environmental sensitivity, with 12-39 cell lines analyzed.

• Why it matters: Understanding cell fitness is crucial for insights into development and disease, but existing methods lack diversity and reproducibility, limiting large-scale genetic studies.
• What they did: They developed a pooled "cell village" screening method with 12-39 genetically distinct human neural progenitor lines and created Townlet, a Dirichlet regression-based statistical framework for analyzing proportional data.
• The result: This approach identified hyperproliferation linked to autism-associated chromosome 16p11.2 deletion, mapped variants near ZFHX3 affecting proliferation, and uncovered genetic modifiers of lead sensitivity, enabling scalable studies of human genetic variation.